Fatty Acid Synthesis Flashcards
Where does fatty acid synthesis occur?
The cytoplasm
What molecule is the building block for fatty acid synthesis?
Acetyl-CoA
Acetyl-CoA is created in the matrix, but fatty acid synthesis occurs in the cytoplasm. How does acetyl-CoA reach the cytoplasm?
Via the citrate shuttle
What are the reactants + products of the citrate shuttle?
1 NADH, 2 ATPs are used
1 NADPH is generated
What are benefits of the citrate shuttle? (3)
- NADPH will be used later on during fatty acid synthesis
- The movement of Acetyl-CoA from the matrix to cytosol is independent of Acetyl-CoA concentration
- Conezyme A is preserved inside the mitochondria (if we had an Acetyl-CoA shuttle, it would be deprived of and this would negatively affect biochemical processes)
What is the function of Acetyl-CoA carboxylase?
It adds a CO2 group to Acetyl-CoA to form Malonyl-CoA
What is the first committed step in fatty acid synthesis?
When ACC is utilized
True or False: The synthesis of Malonyl-CoA through use of ACC is highly exergonic and is essentially irreversible.
True
True or False: Through the use of ATP, HCO3- is added onto biotin in the “biotin carboxylase” domain.
True
True or False: Biotin is carried on the “biotin carboxylase” domain.
False - Biotin is carried on the “biotin carrier protein” domain
True or False: All 3 domains of ACC are found on separate polypeptide chains.
False - All 3 domains of ACC are part of a SINGLE polypeptide chain (Human ACC)
Now that the “biotin carrier protein” domain has CO2 attached to biotin, it swings to the right and bring the reactive CO2 to the ____ ____ where ____ is located.
Active site, Acetyl-CoA
What is the structure of ACC? [Specifically list its size, and the domains it contains.]
- 500kDa dimer
- Contains a biotin carboxylase domain, a biotin carrier protein domain, and a carboxyl-transferase domain
How many active sites are present in ACC?
2 active sites
The reactive CO2 must swing from one active site to another. How much does the BCCP domain have to be rotated?
180 degrees
How many enzymes are required for fatty acid synthase?
6 enzymes
What is the function of the enzyme Thioesterase?
It releases the fatty acid chain from the Fatty Acid Synthase complex
(note - it only engages when the fatty acyl chain reaches 16 C in length!)
What is ACP? What is it attached to?
- Stands for acyl carrier protein
- ACP is covalently attached to a pantothenate cofactor has a reactive SH (thioester) group that carries the growing fatty-acyl group
True or False: In E. Coli, the 6 enzymes are all on separate proteins, while in humans, all enzymes are on a single polypeptide chain.
True! During evolution, all the enzymes combined into a single protein.
True or False: The KS domain has a catalytic cysteine residue (SH).
True
True or False: The ACP domain is linked to the Ketoacyl-Reductase (KR) domain by a long flexible polypeptide segment.
True
What is step 1 of the FAS reaction?
Transacylation: the acetyl group from Acetyl-CoA is added onto the SH group of ACP, then transferred onto the SH group of KS. This opens up space for SH on ACP to accept Malonyl-CoA
What is step 2 of the FAS reaction?
Condensation - CO2 from Malonyl-CoA is removed from ACP and it combines with Acetyl-CoA on the SH of the KS domain
What is significant about step 2 of the FAS reaction?
The release of CO2 drives the reaction forward and makes it irreversible
